POS0452 DIAGNOSTIC AND PROGNOSTIC ROLE OF SERUM KL-6 IN RHEUMATOID ARTHRITIS‑ASSOCIATED INTERSTITIAL LUNG DISEASE
Authors: J. C. Sarmiento-Monroy, A. Pérez-Isidro, R. Castellanos Moreira, V. Ruiz, B. Frade-Sosa, A. Azuaga, J. Ramírez, R. Morlà, A. Ponce Fernandez, P. Corzo Garcia, S. M. Farietta Varela, A. Colmenero, M. Morales-Ruiz, E. Ruiz-Ortiz, O. Viñas, F. Hernández-González, J. Sellarés, J. D. D. Cañete, R. Sanmartí, J. A. Gómez-Puerta
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Interstitial lung disease (ILD) is one of the leading causes of morbidity and premature mortality in rheumatoid arthritis (RA) patients. Some studies have shown that Krebs von den Lungen-6 (KL-6) may be a valuable biomarker for diagnosis and stratifying prognosis in Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD). <h3>Objectives</h3> To evaluate the diagnostic and prognostic value of serum KL-6 in RA-ILD patients. <h3>Methods</h3> We conducted a retrospective study that included patients with RA (ACR/EULAR 2010 criteria) with available KL-6 data measured in blood serum at study enrolment. Patients were evaluated between February 2017 and October 2019 at a single center. ILD was diagnosed by high-resolution computed tomography (HRCT) and confirmed by a multidisciplinary committee. Serum KL-6 levels were measured by Lumipulse G KL-6 Kit (Fujirebio, Japan), using Chemiluminescent enzyme immunoassay (CLEIA). The reference value for KL-6 in healthy subjects was 118-627 U/mL. The inter-assay variation coefficient of the reagent was ≤ 4.4%. We performed a bivariate analysis according to the presence of ILD and high levels of KL-6. Mortality was assessed in December 2022 by medical chart review. <h3>Results</h3> A total of 166 patients were included (36 RA-ILD and 130 RA-non-ILD). Patient baseline characteristics were as follows: female gender 76.5%, mean age 62.9 ± 12.3 years, mean disease duration 9.1 ± 8.7 years, RF positive 66.3%, anti-CCP positive 85.5%, erosive disease 56.0%, and mean DAS28 3.0. The median follow-up period was 5 years (IQR 4.0–5.0). At baseline, patients with RA-ILD were older (69.9 ± 16.1 vs. 60.9 ± 12.3 years; p&lt;0.001), were more frequently males (36.1% vs. 20.0%; p=0.044), had a longer disease duration (12.2 ± 1.3 vs. 8.3 ± 8.7 years; p=0.020), had higher RF titers (412.1 ± 120.5 vs. 165.6 ± 221.1; p&lt;0.001), had a higher disease activity (DAS28 3.7 ± 0.2 vs. 2.8 ± 1.1; p&lt;0.001), and higher mortality (33.3% vs. 9.2%; p&lt;0.001). Among RA-ILD patients at baseline, the median FVC and DLco (% predicted value) were 79 (IQR 72.6–87.0) and 60 (IQR 49.0–70.4), respectively. Usual interstitial pneumonia (UIP) was the predominant pattern at HRCT in half of the patients (18/36). The mean serum KL-6 level at baseline was 513.1 ± 480.1 U/mL. KL-6 levels were abnormally elevated in 35 patients (21.0%). Serum levels of KL-6 in the RA-ILD group were significantly higher than those in the RA-non-ILD group (884.0 ± 134.6 vs. 410.4 ± 262.4 U/mL; p&lt;0.001). Patients with high KL-6 had a higher prevalence of RA-ILD (54.3% vs. 13.0%; p&lt;0.001) and UIP pattern at HRCT (22.9% vs. 7.6%; p&lt;0.001), as well as higher mortality (34.3% vs. 9.2%; p&lt;0.001) (<b>Table 1</b>). During follow-up, 24 (14.5%) patients died, mainly due to respiratory infections (62.5%). The median time to death was 20 months (IQR 7.0–29.0). <h3>Conclusion</h3> Our results suggest that high KL-6 levels might be helpful as a biomarker for diagnosis and prognosis stratification in patients with RA-ILD, especially in patients with UIP pattern at HRCT. <h3>References</h3> [1]Kim HC, et al. <i>PLoS One.</i> 2020 [2]Avouac J, et al. <i>PLoS One.</i> 2020 <h3>Acknowledgements</h3> We want to thank all patients who have participated in the study. Funding: Hospital Clinic of Barcelona (Grant # 37 933) and the Spanish Ministry of Economy and Competitiveness (Grant # RTI2018-094120-B-I00). <h3>Disclosure of Interests</h3> Juan C. Sarmiento-Monroy: None declared, Albert Pérez-Isidro: None declared, Raul Castellanos Moreira Employee of: Bristol-Myers Squibb, Virginia Ruiz: None declared, Beatriz Frade-Sosa: None declared, Ana Azuaga: None declared, Julio Ramírez: None declared, Rosa Morlà: None declared, ANDRES PONCE FERNANDEZ: None declared, PATRICIA CORZO GARCIA: None declared, Sandra Myriam Farietta Varela: None declared, Anna Colmenero: None declared, Manuel Morales-Ruiz: None declared, Estíbaliz Ruiz-Ortiz: None declared, Odette Viñas: None declared, Fernanda Hernández-González: None declared, Jacobo Sellarés: None declared, Juan de Dios Cañete: None declared, Raimón Sanmartí: None declared, José A Gómez-Puerta: None declared.